The CAP will offer in 2012 five new expanded exercises in general chemistry, endocrinology, hematology, and transfusion medicine, with the aim of helping clinical laboratories meet the demands of ever more complex testing. The exercises are not proficiency testing products, and they will be completely voluntary and ungraded. But the CAP believes they will enhance the effectiveness of labs in new ways.

“These expanded exercises are to push people a little further,” says David Sacks, MD, a member of the CAP Chemistry Resource Committee. “They are for labs who say: ‘We know our instruments are fine and we always pass our CAP Surveys, but let’s see if we can do a little better.’”

Katharine A. Downes, MD, vice chair of the CAP Transfusion Medicine Resource Committee, notes that conventional wisdom may call for making assumptions based on probability. “You know the saying, ‘When you hear hoofbeats, think horses, not zebras.’” But in the clinical laboratory, “horse” may not always be the correct assumption. “Labs were expressing an interest in more complexity and challenges that were beyond the scope of standard proficiency testing,” Dr. Downes says. “The expanded exercises are the ‘zebra.’”

The idea for these expanded exercises was conceived more than a year ago, says Alan T. Remaley, MD, PhD, vice chair of the Chemistry Resource Committee. “They’re part of the College’s ongoing effort to get clinical laboratory personnel, particularly at the pathologist level, more engaged in proficiency testing.” Even though the exercises are educational, not regulatory, the laboratory will send its answers back to the College and the CAP will provide the same lab peer evaluations it provides for Surveys.

The five new exercises, covering hormones, lipids, hemoglobin A1c (HbA1c), virtual peripheral blood smear, and transfusion medicine, will join an Expanded Bacteriology exercise that was introduced in 2011. More such exercises are slated. “The plan is to introduce three challenges a year addressing different parts of the lab, so over the course of five years most parts of the lab will be tested. Going forward, our intention is to try to visit almost all clinical lab testing one way or the other,” says Dr. Remaley, who directs the immunoassay laboratory in the Department of Laboratory Medicine, National Institutes of Health.

The Chemistry Resource Committee’s “K cases” program, for which the committee made up clinical situations and generated questions to encourage people to think about their potassium lab test results for the last few years, was a precursor. “That was the genesis of the expanded exercises. We thought we would couple that process with actual challenges,” Dr. Remaley explains. With the new expanded format, “Now we are going to have actual material prepared to fit the particular clinical scenario, so we’re challenging the interpretation as well as the analytical side.” For example, Dr. Remaley notes, when a thyroglobulin test is ordered, it’s strongly recommended that the laboratory also test for the presence of the antibody against thyroglobulin. “In the future, we’ll have Tg testing and we’ll include an antibody that will interfere with the testing. So a lab that does the test measuring anti-Tg as well as Tg will get the right answer, whereas one that doesn’t will give the wrong answer.”

ECE1, the Expanded Hormone exercise, was developed because endocrine hormone results are often challenging to interpret, Dr. Remaley says. “Because of their complexity and sometimes the need to do ancillary tests to make the interpretation, we thought hormone testing would be a good target.”

In the Expanded Lipid exercise (ECE2), the College plans to include case scenarios “that will probe not only the knowledge of the lab in practice but also national guidelines on how to interpret lab results.”

Similarly, the choice was made to focus on HbA1c as another one of the initial expanded exercises, Dr. Remaley says, because the American Diabetes Association recommends it as a first-line test for diabetes.

“There are lots of problems with HbA1c. Some tests will detect it, some don’t. And there are known interferences. We thought an HbA1c expanded exercise would be a good opportunity not only to assess the accuracy of the test but also to develop some questions to make sure people are aware of the ADA guidelines relating to HbA1c.”

In fact, says Dr. Sacks, who is senior investigator at the National Institutes of Health and chief of clinical chemistry for the NIH Department of Laboratory Medicine, the CAP Surveys can take a large share of the credit for the ADA’s embrace of HbA1c for diagnosis of diabetes. Some time ago, the College started sending out whole blood for the HbA1c Surveys, rather than the synthetic products that had been commonly used. With synthetics, there can be matrix effects, making some ingredients in the Survey material interfere with some of the test instruments, which wouldn’t happen with a real patient sample, he explains. Matrix effects result in different instruments producing different results for the same sample. “But if you’re using whole blood, then you can use accuracy-based grading, where everyone’s graded against the true value regardless of the method used.”

“The use of whole blood has improved HbA1c measurement so much that the ADA last year and the World Health Organization this year have accepted HbA1c for diagnosis of diabetes,” he points out, calling this one of the CAP’s most important achievements in influencing patient care. But the most common question addressed to Dr. Sacks, who is chair of the steering committee of the National Glycohemoglobin Standardization Program (NGSP), is about hemoglobin variants S or C, or other hemoglobinopathies. “People ask me, If you test an individual who has variant hemoglobin, can you measure the HbA1c accurately? For example, if somebody measures HbA1c in a patient with a HbAE variant, which is fairly common in some parts of the world and in certain populations in the U.S., they don’t know if the result they are getting is accurate or not, because they may not be aware and often the patients themselves are not aware that they have a variant hemoglobin.” This is a question that interests the NIH because of the public health issues, he adds.

The Expanded HbA1c exercise (ECE3) is intended to determine whether the methods that laboratories use have an interference with the hemoglobin variants. “The manufacturers will say they have tested and something does or doesn’t interfere. But the true way to evaluate, and what really matters, is what happens in the lab that’s measuring the patient sample. That’s the important role that CAP plays: to evaluate the quality of analysis in labs that measure real patient samples.”

Expanding the exercises for the Virtual Peripheral Blood Smear Survey provides a format to set up the complexity of challenges offered, including identification of more difficult cell types and less commonly encountered diagnostic entities, says Joan Etzell, MD, vice chair of the CAP Hematology/Clinical Microscopy Resource Committee and director of the clinical hematology laboratory at the University of California at San Francisco. “With the present proficiency testing Surveys, we’re looking for a fairly high referee concordance rate, and in some ways that has limited the challenges we could do. Previous exercises have been restricted to cell identifications that are relatively commonly encountered. It’s hard to get consensus on the more difficult cell IDs.”

The Expanded Virtual Peripheral Blood Smear exercise (EHE1) will be ready in 2012. “It will be structured to be similar to our Virtual Peripheral Blood Smear Survey, but in addition it will contain some interpretive multiple-choice questions,” Dr. Etzell explains. The Virtual Peripheral Blood Smear Survey is only in its first year, and enrollment has been high, she adds, so she is hopeful that the expanded exercise will be widely used as well.

An important feature of the Expanded Virtual Peripheral Blood Smear exercise is that it will be conducted using DigitalScope, an online technology that developer and CAP partner Proficiency Testing Service refers to as a “Google Earth for slides.”

“A static image of a cell is very different from actually looking at a slide under a microscope,” Dr. Remaley says. “With current technology, the DigitalScope can simulate the experience of having a slide, with computer controls allowing the user to look at different resolutions and actually move around the image to see the whole smear. It’s a much more realistic way to present information.”

Like the Virtual Peripheral Blood Smear Survey itself, the expanded exercise will provide a white blood cell differential, platelet estimate, and red cell morphology, as well as individual cell IDs, Dr. Etzell says. “With a static image, we generally put an arrow on a single cell for cellular identification. Participants are not able to look at the rest of the slide to put the cell in context. With the DigitalScope, not only will there be cellular IDs, but you’ll be able to scan the rest of the slide as well as provide full white cell differentials, a capability that hasn’t been available with the static images. It’s much closer to what’s actually happening at the bench.”

The Expanded Transfusion Medicine exercise (ETME1) is configured to have two challenges twice a year: one wet and one dry for each mailing, says Dr. Downes, associate medical director of blood banking and transfusion medicine, University Hospitals Case Medical Center, Cleveland. “The wet challenges are designed to provide participants with specimens with more complex immunohematological testing challenges than they would have encountered on a typical PT sample.”

These samples may include combinations of tests that are not typically combined in other Surveys. “For example, a type and screen and a titer might be objects of different Surveys, but in the expanded exercise, these would be asked together in one sample set, to apply multiple testing methodologies on one sample.” The “dry” challenges will be based on a patient case and include questions associated with the case, possibly identifications of antibodies and some other situations.

“These are clinical and laboratory testing situations that the participants may encounter infrequently in their daily practice,” Dr. Downes explains. “But knowing how to approach such situations when they do encounter them can be critical. This particular survey may provide new information or a refresher course, or help participants synthesize information they need for complex situations.”

How many laboratories are likely to use the expanded exercises? Dr. Remaley believes the response to the CAP’s newer accuracy-based Surveys may be an indicator. “We have an accuracy-based Survey for lipids and initially we had about 100 participants, but eventually we expect to have about 500 participants. I think the expanded exercises will be even more popular, but I guess time will tell.”

Together, the new expanded exercises offer clinical laboratories a means to advance to the next level of quality. Dr. Downes says, “They will provide a great opportunity for laboratories to have testing material that challenges them with cases that are uncommon and complex.” Dr. Sacks foresees broad benefits as well. “Laboratories that participate in these exercises will be learning a lot about performance of their assays, and they’ll also be contributing to further understanding for manufacturers and patients. So I think the results of these exercises will be very valuable from several aspects.”